The present invention relates to the field of genetic engineering drugs, particularly to a novel B cell activating factor (BAFF) antagonist and use thereof. The technical problem to be solved by the invention is to find a new and effective selection for the prevention and treatment of autoimmune diseases. The B cell activating factor receptor antagonist is mainly obtained by the fusion of the domain 2 binding BAFF in TACI receptor and the domain binding BAFF in Br3 receptor, and it also can be fused with a Fc segment of IgG1 to obtain a new fusion protein molecule. Experiments indicate that said new fusion protein molecule has the function of BAFF antagonist, which can treat the autoimmune diseases, and supply a new and effective selection for the prevention and treatment of the autoimmune diseases.